Difference between revisions of "Phosphatase Subfamily PPP3C"
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__NOTOC__ | __NOTOC__ | ||
| − | [[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_MTDP|Fold MTDP]]: [[Phosphatase_Superfamily_MTDP|Superfamily MTDP]]: [[Phosphatase_Family_PPP|Family PPP]]: [[Phosphatase_Subfamily_PPP3C|Subfamily PPP3C]] | + | [[Phosphatase classification|Phosphatase Classification]]: [[Phosphatase_Fold_MTDP|Fold MTDP]]: [[Phosphatase_Superfamily_MTDP|Superfamily MTDP]]: [[Phosphatase_Family_PPP|Family PPP]]: [[Phosphatase_Subfamily_PPP3C|Subfamily PPP3C]] (PP2B, calcineurin) |
PPP3C, the catalytic subunit of PP2B (calcineurin) holoeynzme, is a calcium-dependent serine/threonine phosphatase conserved in eukaryotes. It is involved in various biological processes and has significantly clinic relevance. | PPP3C, the catalytic subunit of PP2B (calcineurin) holoeynzme, is a calcium-dependent serine/threonine phosphatase conserved in eukaryotes. It is involved in various biological processes and has significantly clinic relevance. | ||
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PPP3C is the catalytic subunit of Protein Phosphatase 2B (PP2B) holoenzyme (aka calcineurin). The holoenzyme is heterodimer complex consisting of one catalytic subunit and one regulatory subunit participates in very various cellular processes, from cell cycle progression to cardiac hypertrophy <cite>Rusnak00</cite>. | PPP3C is the catalytic subunit of Protein Phosphatase 2B (PP2B) holoenzyme (aka calcineurin). The holoenzyme is heterodimer complex consisting of one catalytic subunit and one regulatory subunit participates in very various cellular processes, from cell cycle progression to cardiac hypertrophy <cite>Rusnak00</cite>. | ||
| − | PP2B (calcineurin) activates the T cells of the immune system in mammals. When an antigen-preseting cell interacts with a T cell receptor on T cells, the cytoplasmic level of calcium increases, which activates calcineurin. | + | PP2B (calcineurin) activates the T cells of the immune system in mammals. When an antigen-preseting cell interacts with a T cell receptor on T cells, the cytoplasmic level of calcium increases, which activates calcineurin. PP2B (calcineurin) is used as a target for several immunosuppressive drugs, e.g. [http://en.wikipedia.org/wiki/Tacrolimus tacrolimus] which is an immunosuppressive drug used mainly after allogeneic organ transplant to reduce the activity of the patient's immune system and so lower the risk of organ rejection <cite>Wang15</cite>. |
PP2B (calcineurin) is included as a key player in mediating calcium-triggered and -accelerated vesicle endocytosis <cite>Wu14</cite>. | PP2B (calcineurin) is included as a key player in mediating calcium-triggered and -accelerated vesicle endocytosis <cite>Wu14</cite>. | ||
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This phosphatase has clinical significance for schizophrenia and diabetes (see [http://en.wikipedia.org/wiki/Calcineurin wikipedia]). | This phosphatase has clinical significance for schizophrenia and diabetes (see [http://en.wikipedia.org/wiki/Calcineurin wikipedia]). | ||
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PPP3C (PP2B, calcineurin) modulates potassium channel, perhaps by directly controlling the phosphorylation state of potassium channel in collaboration with PKA <cite>Orie09, Brignell15</cite>. | PPP3C (PP2B, calcineurin) modulates potassium channel, perhaps by directly controlling the phosphorylation state of potassium channel in collaboration with PKA <cite>Orie09, Brignell15</cite>. | ||
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#Orie09 pmid=19422382 | #Orie09 pmid=19422382 | ||
#Rusnak00 pmid=11015619 | #Rusnak00 pmid=11015619 | ||
| + | #Wang15 pmid=25452304 | ||
#Wu14 pmid=24835995 | #Wu14 pmid=24835995 | ||
#Yu15 pmid=25878052 | #Yu15 pmid=25878052 | ||
</biblio> | </biblio> | ||
Revision as of 17:01, 24 April 2015
Phosphatase Classification: Fold MTDP: Superfamily MTDP: Family PPP: Subfamily PPP3C (PP2B, calcineurin)
PPP3C, the catalytic subunit of PP2B (calcineurin) holoeynzme, is a calcium-dependent serine/threonine phosphatase conserved in eukaryotes. It is involved in various biological processes and has significantly clinic relevance.
Evolution
PPP3C is found throughout eukaryotes, including opisthokonta, amoebazoa, plants and etc.
Domain
PPP3C has a single domain - phosphatase domain.
Functions
PPP3C is the catalytic subunit of Protein Phosphatase 2B (PP2B) holoenzyme (aka calcineurin). The holoenzyme is heterodimer complex consisting of one catalytic subunit and one regulatory subunit participates in very various cellular processes, from cell cycle progression to cardiac hypertrophy [1].
PP2B (calcineurin) activates the T cells of the immune system in mammals. When an antigen-preseting cell interacts with a T cell receptor on T cells, the cytoplasmic level of calcium increases, which activates calcineurin. PP2B (calcineurin) is used as a target for several immunosuppressive drugs, e.g. tacrolimus which is an immunosuppressive drug used mainly after allogeneic organ transplant to reduce the activity of the patient's immune system and so lower the risk of organ rejection [2].
PP2B (calcineurin) is included as a key player in mediating calcium-triggered and -accelerated vesicle endocytosis [3].
PP2B (Calcineurin) activates a vertebrate-specific transcription factor called NFATc.
This phosphatase has clinical significance for schizophrenia and diabetes (see wikipedia).
PPP3C (PP2B, calcineurin) modulates potassium channel, perhaps by directly controlling the phosphorylation state of potassium channel in collaboration with PKA [4, 5].
Besides, PPP3C (PP2B, calcineurin) is an attractive antifungal drug target, and its inhibitor (FK506 or cyclosporin A) can be combined with azoles or echinocandins for use against multidrug-resistant Candida species [6].
References
- Rusnak F and Mertz P. Calcineurin: form and function. Physiol Rev. 2000 Oct;80(4):1483-521. DOI:10.1152/physrev.2000.80.4.1483 |
- Wang X, Bi Y, Xue L, Liao J, Chen X, Lu Y, Zhang Z, Wang J, Liu H, Yang H, and Liu G. The calcineurin-NFAT axis controls allograft immunity in myeloid-derived suppressor cells through reprogramming T cell differentiation. Mol Cell Biol. 2015 Feb;35(3):598-609. DOI:10.1128/MCB.01251-14 |
- Wu XS, Zhang Z, Zhao WD, Wang D, Luo F, and Wu LG. Calcineurin is universally involved in vesicle endocytosis at neuronal and nonneuronal secretory cells. Cell Rep. 2014 May 22;7(4):982-8. DOI:10.1016/j.celrep.2014.04.020 |
- Orie NN, Thomas AM, Perrino BA, Tinker A, and Clapp LH. Ca2+/calcineurin regulation of cloned vascular K ATP channels: crosstalk with the protein kinase A pathway. Br J Pharmacol. 2009 Jun;157(4):554-64. DOI:10.1111/j.1476-5381.2009.00221.x |
- Brignell JL, Perry MD, Nelson CP, Willets JM, Challiss RA, and Davies NW. Steady-state modulation of voltage-gated K+ channels in rat arterial smooth muscle by cyclic AMP-dependent protein kinase and protein phosphatase 2B. PLoS One. 2015;10(3):e0121285. DOI:10.1371/journal.pone.0121285 |
- Yu SJ, Chang YL, and Chen YL. Calcineurin signaling: lessons from Candida species. FEMS Yeast Res. 2015 Jun;15(4):fov016. DOI:10.1093/femsyr/fov016 |
